It is impractical to cast ceramics from the molten state as is commonly done with many metal alloys. This is primarily due to the requirement of a highly refined defect free microstructure necessary to produce reliable components with properties for high performance applications. Furthermore the high melting temperature and/or decomposition of the material makes melting impossible or economically impractical.
High performance ceramic materials thus must be made from fine powders that sinter (densify) at a temperature below their melting point. The reduction in free surface energy is the driving force for the elimination of porosity and the densification.
Ceramics are inherently brittle materials and are thus sensitive to flaws which reduce the strength and reliability of the final article. The strength (S) depends on the fracture toughness of the material (KIC) and the size of the flaw or crack (c) as follows: S=YKIC/√{square root over (c)}. The fracture toughness is a material property and Y a geometric factor that depends upon the details of the flaw shape. Large flaws and cracks greatly reduce tile strength of the material.
Current forming processes such as dry pressing result in inhomogeneous green density, which results in flaws that reduce strength and reliability. The dry processing technique is deficient in that there is no capacity to de-agglomerate the dry powder and remove flaws from the powder that may exist in the as received raw material, or were accidentally added to the powder during processing.
Wet colloidal processing can be used to overcome the deficiencies of dry powder processing. The colloidal method may be used to break down agglomerates and remove flaws via filtration, sedimentation or other means to produce nearly defect free uniform density green bodies. This results in improved strength and reliability of the final component (Lange 1989, Pujari 1995).
Ceramics are extremely hard materials and thus are difficult to machine. Expensive diamond grinding is often required in order to finish articles produced by known methods. Thus it is economically advantageous to produce a component which does not require, or requires only minimal machining. Processes which do not require machining after forming of the shaped article are known as net shape processes and constitute the most desirable approach.
Several methods of producing near net shaped ceramic and metal articles from powders currently exist. Although useful for some applications many of these processes have some disadvantages compared to the present invention.
Thermoplastic injection of powders with binders that melt have been known for more than 30 years (U.S. Pat. No. 3,351,688). These methods utilise binders such as paraffin wax (U.S. Pat. No. 4,011,291), thermoplastic polymeric resins (U.S. Pat. No. 4,144,207), and more recently polymer mixtures (U.S. Pat. No. 4,571,414) which are molten at high temperature and solidify at lower temperature within the mould cavity. These methods have several limitations and problems. Firstly, since they solidify upon cooling the part may slump or loose its shape on the further reheating needed for binder removal and sintering. The removal or burnout of the large quantities of binders used in these methods generally results in lengthy and costly heat treatments, cracking, distortion, and generally low quality components (German et al. 1991). Furthermore, many of these processes utilise equipment originally designed for plastics manufacture. The use of abrasive ceramic particles in these metal devices which are operated under high pressure, results in wear of the equipment and detrimental metallic inclusions in the article. Systems that utilise thermosetting binders such as epoxies (U.S. Pat. No. 2,939,199, U.S. Pat. No. 4,456,713, Takeshita et al. 1997) suffer from many of the same problems, particularly including lengthy and detrimental binder burnout processes.
Low pressure injection moulding (Mangels 1994) processes may alleviate at least the abrasion problem associated with the high pressure injection moulding processes, but by itself does not address the binder problems. The Quickset injection moulding process, (U.S. Pat. Nos. 5,047,181, 5,047,182) utilises a low pressure injection moulding (or pourable) process with only a few percent of a binder in either aqueous or non-aqueous solvents. This method utilises the freezing of the suspending medium as the method of changing the suspension behaviour from liquid-like to solid-like. This system has the advantage that the solidification can occur very quickly. The disadvantage of this system is that it requires a lengthy and costly (sublimative) freeze drying process since the parts would melt and lose shape if heated under atmospheric pressure during drying. The advantage of the above mentioned thermoplastic and low pressure injection moulding formulations is that temperature may be used as a switch mechanism for controlling the suspension behaviour as either a liquid-like or a solid-like maternal.
Recently another pourable or low pressure injection mouldable process which utilises an aqueous system has been disclosed (U.S. Pat. Nos. 5,667,548, 5,788,891, 5,948,335, Balzer et al., 1999). This method relies on a chemically activated change in solution conditions that change the particle-particle interaction from repulsive to attractive. This process requires particularly long retention times in the mould to achieve strength sufficient to successfully remove the mould. The published results indicate that it takes 24 hours for the articles to achieve a strength of about 8 kPa. (Balzer et al. 1999) With this system, once all the components are added to the suspension the gelation begins and proceeds even at room temperature, although the rate is much slower than when the temperature is increased. In practice it is difficult to produce a suspension which will remain liquid-like for a sustained period at room temperature, and gel quickly at elevated temperature.
Janney and coworkers (U.S. Pat. Nos. 4,894,194, 5,028,362, 5,145,908) disclose a process which utilises the polymerisation of a monomer in the suspension solution via a free radical initiator. This process produces strong de-mouldable bodies relatively quickly. There is only a relatively small amount of the polymer in the green body (article before firing) so it is relatively easy to burn out. Unfortunately most of the monomer-initiator systems suitable for the process are somewhat toxic. The mechanical behaviour of bodies produced with this method indicate very limited flexibility and thus may be fractured when large strains arc applied to the component during de-moulding.
Methods suitable for filling moulds via low pressure injection moulding or pouring that utilise aqueous solutions of gelling bio-polymers have also been disclosed. These methods (U.S. Pat. Nos. 4,734,237, 5,286,767, 5,503,771, Chen et al. 1999,) generally utilise physical gelation of bio-polymers such as agar, alginate, gelatine, or pectin. These systems gel when the temperature is decreased, and the gelation is reversible. The disadvantage of these types of systems is that they will re-liquefy when heated again for instance during drying and sintering of the part. The method disclosed by Rivers (U.S. Pat. No. 4,113,480) utilises methylcellulose, which gels as the temperature is increased. All these methods rely on the gelation to proceed by a mechanism in which the polymer chains form intertwined coils held together by physical bonds. With these methods the polymer chains are not chemically cross-linked.
No previously disclosed method describes a polymer cross-linked with a temperature activated cross-linking agent for forming shaped articles, particularly from powders. Although the invention was originally conceived in the context of ceramic gel casting, the present inventors have also found application for their work in the production of pharmaceutical controlled release formulations and shaped articles containing other components. The present invention allows the encapsulation of pharmaceutical substances which can be released at a controlled rate following administration. The adoption of this technology in the preparation of pharmaceutical controlled release formulations has the advantage of allowing thorough mixing of the pharmaceutical substance within the gel forming mixture with the ability to readily manipulate gel strength and thus also the rate of pharmaceutical substance release.
It is with the above background in mind that the present invention has been conceived.